Triple adjuvant therapy with transarterial chemoembolizaition, lenvatinib, and programmed death-1 inhibitors improves short-term recurrence control in high-risk patients with resected intermediate-stage hepatocellular carcinoma

Background Intermediate-stage hepatocellular carcinoma (HCC) following curative liver resection (LR) is associated with high recurrence rates and poor survival outcomes. Current studies have found that transarterial chemoembolization can improve overall survival rates and disease free survival in patients with intermediate-stage HCC after surgery. However, the benefits of this treatment are limited. This study aimed to evaluate the benefit of triple adjuvant therapy—transarterial chemoembolization (TACE) combined with antiangiogenic therapy (lenvatinib) plus programmed death-1 inhibitors (TAP)—as an adjuvant treatment for resected intermediate-stage HCC, compared to TACE alone, and to identify patient subgroups most likely to benefit from the TAP regimen. Materials and methods We collected data of patients with intermediate-stage HCC who underwent LR from December 2019 to December 2022. Disease-free survival (DFS) was compared between patients receiving TACE and those receiving TAP using propensity score matching. The 2-year recurrence rate in the entire cohort was predicted based on the TACE group, and the association between the predicted and observed recurrences was tested. Outcomes A total of 571 patients were included in our study, with 102 receiving TAP and 469 receiving TACE. Compared with TACE alone, TAP showed better DFS (HR: 0.74; 95% CI: 0.56–0.98; P = 0.037), with median: 22.0 months (95% CI: 19.0–24.0) vs 25.6 months (95% CI: 24.0–40.0). The lines for the TACE and TAP intersected at 37% indicating that patients with a predicted 2-year recurrence risk >37% would significantly benefit from TAP. TAP therapy demonstrated a manageable AE profile, an overall AEs of 79.4%, with grade 1-2 accounting for 65.7%, grade 3 for 11.8%, and grade 4 for 1.9%. Conclusions: TAP therapy demonstrated significant potential as an adjuvant treatment for intermediate-stage HCC following curative resection, offering superior recurrence control and survival benefits compared to TACE alone. Patients with a predicted recurrence risk >37% showed improved DFS outcomes in TAP therapy, suggesting that recurrence risk thresholds could guide tailored treatment decisions in clinical practice. The manageable safety profile of TAP further supports its feasibility in the postoperative setting.Our findings represent a substantial advancement in the field of adjuvant therapy for resected intermediate-stage HCC.